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The purpose of this study was to investigate the influence of increasing sulfate concentrations on chromium removal, to evaluate the effect of the presence of Cr(VI) on sulfate removal by Streptomyces sp. MC1 and to analyze the differential protein expression profile in the presence of this metal for the identification of proteins repressed or overexpressed. In the presence of Cr(VI) but in the absence of sulfate ions, bacterial growth was negligible, showing the Cr(VI) toxicity for this bacterium. However, the sulfate presence stimulated bacterium growth and Cr(VI) removal, regardless of its concentrations. Streptomyces sp. MC1 showed ability to remove chromium and sulfate simultaneously. Also, the sulfate presence favored the decrease of total chromium concentration from supernatants reaching a decrease of 50% at 48 h. In presence of chromium, seven proteins were down‐expressed and showed homology to proteins involved in protein biosynthesis, energy production and free radicals detoxification while two proteins involved in oxidation‐reduction processes identified as dihydrolipoamide dehydrogenase and S‐adenosyl‐l‐methionine synthase were overexpressed.

Ethanol has been claimed to potentiate greatly the lethality of propoxyphene, although published clinical data suggest only an additive effect. Mice were treated intraperitoneally with various doses of propoxyphene hydrochloride and ethanol. Isobolograms of the data show the combination to be less-than-additive for lethality and loss of motor coordination and, at worst, simply additive for sedation.

Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue.

Ethanol is associated with oxidative stress. Exposure to ethanol during childhood may lead to neurological disorders. Congenital disorders induced by alcohol are mainly caused by an oxidative-inflammatory cascade due to extensive apoptotic neurodegeneration in the brain, particularly in the hippocampus. Simvastatin, which acts as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), is widely used to manage cardiovascular diseases. Recently, the neuroprotective effects of simvastatin against nervous system disorders have been introduced. In this study, we examined the protective effects of simvastatin on ethanol-related neurotoxicity in the hippocampus of rat pups. Ethanol (5.27 g/kg) in a milk solution (27.8 mL/kg) was administered to male rat pups via intragastric intubation at 2-10 days after birth. Also, 10 and 20 mg/kg of simvastatin were injected to the animals. By using Morris water maze task, the hippocampus-dependent memory and spatial learning was evaluated 36 days after birth. An ELISA assay was performed to investigate the antioxidant and anti-inflammatory effects of simvastatin by measuring the levels of tumor necrosis factor-α (TNF-α), and antioxidant enzymes. To assess the expression levels of Iba1 immunohistochemical staining and caspase-3 immunofluorescence staining was performed. The current study demonstrated that administration of simvastatin significantly attenuates spatial memory impairment (P < 0.01) after ethanol neurotoxicity. Also simvastatin could considerably increase the total superoxide dismutaseand glutathione levels (P < 0.01). Moreover, it was associated with a greater reduction in malondialdehyde (P < 0.05) and TNF-α levels, compared to the ethanol group (P < 0.01). Furthermore, in the simvastatin group, the hippocampal level of caspase-3 and the level of Iba1-positive cells, reduced (P < 0.01). This study demonstrated that apoptotic signaling, mediated by the oxidative-inflammatory cascade, could be inhibited by simvastatin in rat pups with ethanol exposure in the postnatal period.

Alcoholism is associated with a higher incidence of smoking. In addition to the stimulatory effects of both ethanol and nicotine on the mesolimbic reward pathway, nicotine's ability to counteract some of the adverse effects of ethanol (e.g. ataxia) may be a powerful incentive for alcohol consumers to increase their tobacco (nicotine) intake. The cerebellum is believed to play an important role in ethanol-induced ataxia. In this study, we sought to test the hypothesis that nicotine would protect against toxic effects of ethanol in primary cultures of cerebellar granule cells. Moreover, it was postulated that the effects of nicotine would be mediated through nicotinic receptors. Primary cultures of cerebellar granule cells were prepared from 20-day embryos obtained from timed-pregnant Sprague Dawley rats. Cells were cultured for 10 days and were then exposed for 3 days to various concentrations of ethanol with and without pretreatment with nicotine and nicotinic antagonists. Cellular toxicity was evaluated by measuring the lactate dehydrogenase level. Administration of ethanol (10-100 mM) resulted in a dose-dependent toxicity. Pretreatment with nicotine 1-20 micro M resulted in a dose-dependent protection against ethanol-induced toxicity. The effects of nicotine were blocked by pretreatment with nicotinic antagonists such as mecamylamine 1-20 micro M, dihydro-beta-erythroidine 1.0 nM-1.0 micro M and methyllycaconitine 5 nM-5 micro M in a dose-dependent manner. Thus, ethanol-induced cytotoxicity in primary cultures of cerebellar granule cells is blocked by pretreatment with nicotine. The effects of nicotine, in turn, may be blocked by nicotinic antagonists, implicating both high and low affinity nicotinic receptors in mediating the actions of nicotine. The exact mechanism of ethanol-induced toxicity and/or neuroprotection through activation of nicotinic receptors in this paradigm remains to be elucidated. The neuroprotective effect of nicotine against ethanol-induced toxicity in cerebellar neurons may be a contributing factor to the high incidence of smoking among alcoholics.

Background: Most of the studies of alcoholic liver disease use models in which animals undergo involuntary administration of high amounts of ethanol and consume diets that are often high in polyunsaturated fatty acids. The objectives of this study were (1) to evaluate whether cynomolgus monkeys (Macaca fascicularis) drinking ethanol voluntarily and consuming a diet with moderate amounts of lipid would demonstrate any indices of alcoholic liver disease past the fatty liver stage and (2) to determine whether these alterations were accompanied by oxidative stress.Methods: Six adult male and 6 adult female cynomolgus monkeys were allowed to consume ethanol voluntarily for 18 to 19 months. Additional monkeys were maintained on the same consumption protocol, but were not provided with ethanol. During the course of the study, liver biopsy samples were monitored for lipid deposition and inflammation, serum for levels of liver enzymes, and urine for concentrations of the isoprostane (IsoP) metabolite, 2,3‐dinor‐5,6‐dihydro‐15‐F2t‐IsoP, a biomarker for oxidative stress. Liver mitochondria were monitored for respiratory control and liver for concentrations of neutral lipids, adenine nucleotides, esterified F2 isoprostanes, oxidized proteins, 4‐hydroxynonenal (HNE)‐protein adducts, and protein levels of cytochrome P‐450 2E1 and 3A4.Results: Ethanol consumption ranged from 0.9 to 4.05 g/kg/d over the period of the study. Serum levels of aspartate amino transferase were elevated in heavy‐consuming animals compared with those in ethanol‐naïve or moderate drinkers. Many of the ethanol consumers developed fatty liver and most showed loci of inflammation. Both hepatic energy charge and phosphorylation potential were decreased and NADH‐linked respiration was slightly, but significantly depressed in coupled mitochondria as a result of heavy ethanol consumption. The urinary concentrations of 2,3‐dinor‐5,6‐dihydro‐15‐F2t‐IsoP increased as high as 33‐fold over that observed in ethanol‐abstinent animals. Liver cytochrome P‐450 2E1 concentrations increased in ethanol consumers, but there were no ethanol‐elicited increases in hepatic concentrations of the esterified F2 isoprostanes, oxidized proteins, or HNE‐protein adducts.Conclusion: Our studies show that cynomolgus monkeys undergoing voluntary ethanol consumption for 1.5 years exhibit many of the features observed in the early stages of human alcoholic liver disease. Ethanol‐elicited fatty liver, inflammation, and elevated serum aspartate amino transferase were evident with a diet that contained modest amounts of polyunsaturated lipids. The dramatic increases in urinary IsoP demonstrated that the animals were being subjected to significant oxidative stress that correlated with their level of ethanol consumption.

Changes or imbalances in plasma amino acid patterns during withdrawal from ethanol were recorded in six randomly selected male chronic alcoholic patients (age range 23-47 years). Duration of drinking ranged from 4-15 years and their average daily amount of ethanol intake was more than 100G. Plasma amino acids (taurine, threonine, serine, glutamate, glutamine, proline, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, tryptophan, ornithine, lysine and arginine) were estimated by autoanalyzer in all patients on admission before starting conventional detoxification therapy for ethanol withdrawal syndrome, and during therapy on day 3 and day 6. On admission, there was a statistically significant rise in the plasma levels of almost all aminoacids, particularly glutamate, glutamine, phenylalanine, proline, glycine, methionine, cysteine, lysine, tyrosine, valine, isoleucine, leucine, serine, threonine, alanine and arginine (in comparison to those of normal controls) in five out of six patients. During the following six days of treatment and total abstinence, the pattern of plasma aminoacid levels did not change significantly despite considerable clinical improvement. Plasma tryptophan levels were undetectable in all patients on admission, day 3 and also on day 6 except in one patient with lesser amount and shorter duration of drinking, the levels just returned to within normal range only on day 6. Plasma levels of histidine and taurine were found to be slightly lower than normal.

Chronic alcohol consumption induces myocardial damage and a type of non-ischemic cardiomyopathy termed alcoholic cardiomyopathy, where mitochondrial ultrastructural damages and suppressed fusion activity promote cardiomyocyte apoptosis. The aim of the present study is to determine the role of mitochondrial fission proteins and/or other proteins that localise on cardiac mitochondria for apoptosis upon ethanol consumption. In vivo and in vitro chronic alcohol exposure increased mitochondrial Drp1 levels but knockdown of the same did not confer cardioprotection in H9c2 cells. These cells displayed downregulated expression of MFN2 and OPA1 for Bak-mediated cytochrome c release and apoptosis. Dysregulated PTEN/AKT cell survival signal in both ethanol treated and Drp1 knockdown cells augmented oxidative stress by promoting mitochondrial PTEN-L and MFN1 interaction. Inhibiting this interaction with VO-OHpic, a reversible PTEN inhibitor, prevented Bak insertion into the mitochondria and release of cytochrome c to cytoplasm. Thus, our study provides evidence that Drp1-mediated mitochondrial fission is dispensable for ethanol-induced cardiotoxicity and that stress signals induce mitochondrial PTEN-L accumulation for structural and functional dyshomeostasis. Our in vivo results also demonstrates the therapeutic potential of VO-OHpic for habitual alcoholics developing myocardial dysfunction.

Anaphylactic reactions to ethanol are rare with only seven cases reported in the literature. All previous cases have occurred following ingestion of alcoholic beverages or food to which an alcoholic beverage has been added. To date there are no cases in the literature of ethanol-induced anaphylaxis caused by the accumulation of endogenous ethanol in overripe fruit.We report a patient with ethanol-induced anaphylaxis who developed anaphylaxis following ingestion of overripe, but not fresh rock melon (Cucumis melo). The patient is a 24-year-old, previously well woman who experienced five episodes of acute anaphylaxis following ingestion of various alcoholic beverages and, on one occasion, following ingestion of overripe rock melon to which no ethanol was added. Ethanol-induced anaphylaxis was confirmed on blinded challenge; however, challenge with freshly prepared rock melon was negative. The patient declined further challenges.Ingestion of overripe fruits may cause anaphylaxis in patients with ethanol-induced anaphylaxis. These patients should therefore, be advised to avoid ingestion of overripe fruits.